FXa inhibition and coagulation changes during DVT prophylaxis by enoxaparin over the course of a 15-day follow-up in septic patients

Clin Appl Thromb Hemost. 2010 Oct;16(5):584-90. doi: 10.1177/1076029609345686. Epub 2009 Oct 22.

Abstract

The objective of our study was to examine the changes in coagulation parameters and inflammatory reaction over the course of 15 days in patients with severe sepsis. We tried to identify mechanisms by which sepsis-induced pathophysiological changes may influence the effectiveness of subcutaneously (SC) administered enoxaparin 40 mg once daily. A total of 16 patients (8 men, 8 women; age 35-83 years) meeting the inclusion criteria of severe sepsis were enrolled in this study. The follow-up was performed on days 1, 2, 3, 6, 9, 12, and 15 of hospitalization at the intensive care unit (ICU). Blood coagulation (activated partial thromboplastin time [aPTT], prothrombin time [PT], fibrinogen, antithrombin (AT), protein C [PC], D-dimer, fragment 1.2 [F1.2], factor Xa [FXa] inhibition) and inflammatory reactants (interleukin 6 [IL-6], C-reactive protein [CRP], orosomucoid, alpha-1-antitrypsin) were tested. The mean FXa inhibition was 0.17 (+ or - 0.17) IU/mL. The arbitrarily established range of FXa inhibition for prophylaxis, 0.2 to 0.4 IU/mL, was reached in 22 cases (20%), while in 74 cases (68%), it was below and in 13 cases (12%) above the aforementioned range. Factor Xa inhibition positively correlated with AT (r = .42; P < .001) and PC (r = .45; P < .001) activities. A negative correlation was found between the FXa inhibition and alpha-1-antitrypsin concentrations (r = -.33; P = .01) but only in the subgroup with alpha-1-antitrypsin concentrations > or = 2.2 g/L. We confirmed that in most patients with sepsis, the prophylaxis with enoxaparin did not lead to the required FXa inhibition. The inhibition of FXa by enoxaparin depends mainly on the AT and PC activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use*
  • Blood Coagulation / drug effects*
  • Enoxaparin / therapeutic use*
  • Factor Xa Inhibitors*
  • Humans
  • Male
  • Middle Aged
  • Sepsis / blood*
  • Venous Thrombosis / blood*
  • Venous Thrombosis / prevention & control*

Substances

  • Anticoagulants
  • Enoxaparin
  • Factor Xa Inhibitors